The broad objective of this application is to establish that the endogenous cardiac peptide B-type natriuretic peptide (BNP) is a novel and efficacious protein therapeutic for human acute myocardial infarction (AMI) to preserve myocardial structure and function reducing ultimately the burden of human heart failure (HP). This highly translational research builds upon ongoing basic and clinical research pursued by the applicants and currently supported by HL83231 (Cardiac Peptides in Myocardial Infarction). Our application specifically takes advantage of the cardioprotective properties of this small and endogenous myocardial peptide in protecting the heart from injury and promoting cardiac repair. Our therapeutic strategy is based upon the emerging biology of BNP, which goes beyond renal actions and includes direct actions on cardiomyocytes and non-myocyte cardiac cells. The Specific Aims are as follows: Aim 1: To collect clinical outcome data beyond the 30 days follow up in the pilot human study supported by HL83231 so as to use this data to calculate sample size and power calculation for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. Aim 2: Organize the Scientific Advisory Board and Steering Committee consisting of both scientists and clinical experts to draft the plan for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial." We will also organize the Data and Safety Monitoring Board (DSMB). Aim 3: Engage a clinical research organization (CRO) to begin plans for site recruitment and regulatory management of the proposed multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" that will be supported by the F50 program. Aim 4: To engage the FDA in amending our investigator held IND for the use of BNP in human myocardial infarction to include our multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. We believe that our proposal meets the objectives of the C-TRIF P20 Program and accelerates translation of promising new therapeutic interventions such as BNP for AMI to reduce the burden of future HF. RELEVANCE (See instructions): Chronic heart failure (CHF) is a clinical syndrome with significant mortality and morbidity despite recent advances in the understanding of the pathophysiology and treatment. The latest figures from the American Heart Association reports a prevalence of 5 million with incidence of 550,000 cases, annual mortality of 52,000 and a total cost of 28 billion dollars in healthcare expense per year in the US. This research will aid in addressing this health challenge.